Objective:To evaluate the clinical value of DH3 human papilloma virus(HPV)DNA and Aptima HPV E6/E7 mRNA testing in detecting cervical lesions.Methods:Retrospective analysis included 1254 cases test-ed with DH3-HPV DNA and 8263 cases tested with Aptima HPV E6/E7 mRNA from January 1,2022 to December 31,2023 at Women's Hospital,School of Medicine,Zhejiang University.All patients have follow-up re-sults of cervical biopsy pathology.Cervical biopsy histopathology served as the gold standard.The sensitivity and specificity for detecting low-grade squamous intraepithelial lesion and higher cervical lesions(LSIL+)or high-grade squamous intraepithelial lesion and higher cervical lesions(HSIL+)were compared between the two meth-ods.Results:The positive prevalence was 75.44%(946/1254)in DH3-HPV DNA testing,and 79.29%(6552/8263)in Aptima HPV E6/E7 mRNA testing.In women older than55 years,Aptima HPV E6/E7 mRNA showed a higher positive rate than that of DH3-HPV DNA[84.70%(1583/1869)vs.76.34%(200/262),P<0.05).The sensi-tivity of DH3-HPV DNA and Aptima HPV E6/E7 mRNA detection of LSIL+was 90.63%(493/544)and 91.79%(2953/3217),respectively,with no statistically significant difference(P>0.05).The specificity of DH3-HPV DNA and Aptima HPV E6/E7 mRNA 16/18 geneotyping detection using LSIL+was 83.94%(596/710)and 85.67%(4323/5046),respectively,with no statistically significant difference(P>0.05).The sensitivity of DH3-HPV DNA and Aptima HPV E6/E7 mRNA detection for HSIL+lesions was 93.94%(124/132)and 97.51%(782/802),respectively,with no statistically significant difference(P>0.05).The specificity of Aptima HPV E6/E7 mRNA 16/18/45 geneotyping detection using HSIL+was 83.50%(6230/7461),significantly higher than that of DH3-HPV DNA 16/18 geneotyping detection at 81.02%(909/1122),with statistically significant difference(P<0.05).Conclusions:The sensitivity of DH3-HPV DNA and Aptima HPV E6/E7 mRNA in the detection of cervical lesions is similar.Aptima HPV E6/E7 mRNA geneotyping has a high specificity in the detection of HSIL+than DH3-HPV DNA geneotyping.The higher positive prevalence of Aptima HPV E6/E7 mRNA in women older than 55 years may reflect increased HPV integration rates in this population.

Objective:To investigate the role of the Smad3 signaling pathway in the process of silica-induced epithelial-mesenchymal transition (EMT) .Methods:In September 2022, lung epithelial cells (BEAS-2B) were exposed to different concentrations of silica suspension (0, 50, 100, and 150 μg/ml) for 6 and 12 hours. Additionally, SIS3, a specific inhibitor of phosphorylated Smad3 (p-Smad3) , was utilized to establish the p-Smad3 inhibition model. The cells were divided into four groups: blank control gruop, silica group, SIS3 intervention group, and SIS3 +silica group. Cell morphology was observed using an inverted fluorescence microscope, while cell viability was assessed using a Cell Counting Kit-8 (CCK-8) . The mRNA and protein expression levels of E-cadherin (E-Cad) , N-cadherin (N-Cad) , Vimentin, Smad3, and p-Smad3 were analyzed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Differences between two groups were compared using Student's t-test, and multiple group comparisons were analyzed using a one-way analysis of variance with the Student-Newman-Keuls test.Results:Compared with the blank control group, the morphology of BEAS-2B cells shifted from epithelial to mesenchymal cell-like following silica exposure, and the cell viability of BEAS-2B cells declined after exposure to 150 μg/ml silica for 6 and 12 hours. Furthermore, silica exposure led to significant reductions in mRNA and protein expression levels of the epithelial cellular marker (E-Cad) in BEAS-2B cells, accompanied by increased expressions of interstitial cellular markers (N-Cad and Vimentin) . Importantly, the level of p-Smad3/Smad3 expression levels was also elevated in silica-treated cells ( P<0.05) . Compared to the blank control group, the level of p-Smad3/Smad3 expression levels was significantty reduced. Moreover, compared to the silica group, the protein expression levels of N-Cad and Vimentin in the cell of the SIS3+silica group were significantly reduced, while the E-Cad expression was increased ( P<0.05) . Conclusion:Silica exposure can prmote the epithelial mesenchymaol transformotion process by activating smod3 signa ling pathuay, and in hibiting smad3 signa ling pathuay can effctively alleviate the occurrence of epithelial mesenchymal transformation process.

OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

Objective: To investigate the current status and influencing factors for cognitive frailty among the elderly in community, so as to provide the evidence for early identification and prevention of cognitive frailty among the elderly. Methods: Residents aged 60 years and above with local household registration from 11 counties (cities, districts) in Zhejiang Province from 2021 to 2023 were selected as study participants using a multistage random sampling method. Demographic information, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were assessed using the Patient Health Questionnaire. Cognitive frailty was evaluated using the FRAIL Scale and the Mini-Mental State Examination. Factors affecting cognitive frailty among the elderly in community were identified using a multivariable logistic regression model. Results: A total of 16 613 individuals were surveyed, including 7 465 males (44.93%) and 9 148 females (55.07%). The average age was (70.97±7.29) years. A total of 784 individuals were detected with depressive symptoms, with a detection rate of 4.72%. A total of 724 individuals were detected with cognitive frailty, with a detection rate of 4.36%. Multivariable logistic regression analysis showed that females (OR=1.419, 95%CI: 1.179-1.708), aged ≥70 years (70-<80 years old, OR=1.869, 95%CI: 1.490-2.345; ≥80 years old, OR=5.017, 95%CI: 3.935-6.398), without a spouse (OR=1.495, 95%CI: 1.234-1.810), sedentary (OR=2.420, 95%CI: 1.829-3.202), chronic diseases (1 type, OR=1.456, 95%CI: 1.175-1.804; ≥2 types, OR=1.639, 95%CI: 1.314-2.045), and depressive symptoms (OR=4.191, 95%CI: 3.361-5.225) were associated with a higher risk of cognitive frailty among the elderly in community. Conversely, a lower risk of cognitive frailty was seen among the elderly in community who had primary school or above (primary school, OR=0.512, 95%CI: 0.389-0.676; junior high school or above, OR=0.464, 95%CI: 0.354-0.608), engaged in physical exercise (OR=0.396, 95%CI: 0.291-0.539), and were reported average or good self-rated health status (average, OR=0.641, 95%CI: 0.475-0.866; good, OR=0.150, 95%CI: 0.109-0.208). Conclusions The detection rate of cognitive frailty among the elderly in community is relatively low and is influenced by demographic factors such as gender, age, education level, as well as lifestyle like sedentary and physical exercise, and health status. It is recommended to reduce the risk of cognitive frailty among the elderly through multidimensional interventions, including health education, promotion of healthy lifestyles, and enhanced mental health support.

Objective:To evaluate the clinical value of DH3 human papilloma virus(HPV)DNA and Aptima HPV E6/E7 mRNA testing in detecting cervical lesions.Methods:Retrospective analysis included 1254 cases test-ed with DH3-HPV DNA and 8263 cases tested with Aptima HPV E6/E7 mRNA from January 1,2022 to December 31,2023 at Women's Hospital,School of Medicine,Zhejiang University.All patients have follow-up re-sults of cervical biopsy pathology.Cervical biopsy histopathology served as the gold standard.The sensitivity and specificity for detecting low-grade squamous intraepithelial lesion and higher cervical lesions(LSIL+)or high-grade squamous intraepithelial lesion and higher cervical lesions(HSIL+)were compared between the two meth-ods.Results:The positive prevalence was 75.44%(946/1254)in DH3-HPV DNA testing,and 79.29%(6552/8263)in Aptima HPV E6/E7 mRNA testing.In women older than55 years,Aptima HPV E6/E7 mRNA showed a higher positive rate than that of DH3-HPV DNA[84.70%(1583/1869)vs.76.34%(200/262),P<0.05).The sensi-tivity of DH3-HPV DNA and Aptima HPV E6/E7 mRNA detection of LSIL+was 90.63%(493/544)and 91.79%(2953/3217),respectively,with no statistically significant difference(P>0.05).The specificity of DH3-HPV DNA and Aptima HPV E6/E7 mRNA 16/18 geneotyping detection using LSIL+was 83.94%(596/710)and 85.67%(4323/5046),respectively,with no statistically significant difference(P>0.05).The sensitivity of DH3-HPV DNA and Aptima HPV E6/E7 mRNA detection for HSIL+lesions was 93.94%(124/132)and 97.51%(782/802),respectively,with no statistically significant difference(P>0.05).The specificity of Aptima HPV E6/E7 mRNA 16/18/45 geneotyping detection using HSIL+was 83.50%(6230/7461),significantly higher than that of DH3-HPV DNA 16/18 geneotyping detection at 81.02%(909/1122),with statistically significant difference(P<0.05).Conclusions:The sensitivity of DH3-HPV DNA and Aptima HPV E6/E7 mRNA in the detection of cervical lesions is similar.Aptima HPV E6/E7 mRNA geneotyping has a high specificity in the detection of HSIL+than DH3-HPV DNA geneotyping.The higher positive prevalence of Aptima HPV E6/E7 mRNA in women older than 55 years may reflect increased HPV integration rates in this population.

Objective:To investigate the role of the Smad3 signaling pathway in the process of silica-induced epithelial-mesenchymal transition (EMT) .Methods:In September 2022, lung epithelial cells (BEAS-2B) were exposed to different concentrations of silica suspension (0, 50, 100, and 150 μg/ml) for 6 and 12 hours. Additionally, SIS3, a specific inhibitor of phosphorylated Smad3 (p-Smad3) , was utilized to establish the p-Smad3 inhibition model. The cells were divided into four groups: blank control gruop, silica group, SIS3 intervention group, and SIS3 +silica group. Cell morphology was observed using an inverted fluorescence microscope, while cell viability was assessed using a Cell Counting Kit-8 (CCK-8) . The mRNA and protein expression levels of E-cadherin (E-Cad) , N-cadherin (N-Cad) , Vimentin, Smad3, and p-Smad3 were analyzed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Differences between two groups were compared using Student's t-test, and multiple group comparisons were analyzed using a one-way analysis of variance with the Student-Newman-Keuls test.Results:Compared with the blank control group, the morphology of BEAS-2B cells shifted from epithelial to mesenchymal cell-like following silica exposure, and the cell viability of BEAS-2B cells declined after exposure to 150 μg/ml silica for 6 and 12 hours. Furthermore, silica exposure led to significant reductions in mRNA and protein expression levels of the epithelial cellular marker (E-Cad) in BEAS-2B cells, accompanied by increased expressions of interstitial cellular markers (N-Cad and Vimentin) . Importantly, the level of p-Smad3/Smad3 expression levels was also elevated in silica-treated cells ( P<0.05) . Compared to the blank control group, the level of p-Smad3/Smad3 expression levels was significantty reduced. Moreover, compared to the silica group, the protein expression levels of N-Cad and Vimentin in the cell of the SIS3+silica group were significantly reduced, while the E-Cad expression was increased ( P<0.05) . Conclusion:Silica exposure can prmote the epithelial mesenchymaol transformotion process by activating smod3 signa ling pathuay, and in hibiting smad3 signa ling pathuay can effctively alleviate the occurrence of epithelial mesenchymal transformation process.

Pain is a prevalent symptom in both cancer and non-cancer end-stage diseases, often being the most feared by patients and significantly impacting their quality of life.Hospice care aims to address physical, psychological, spiritual, and other needs of patients and their families during this stage, with a focus on alleviating pain and discomfort.Effective pain management is a crucial component of hospice care, particularly given the increasing prevalence of cancer and chronic diseases in China and the growing elderly population.To provide analgesic management for hospice patients, a thorough assessment of pain is essential to identify its type and characteristics.Treatment approaches may include etiological interventions, pharmacotherapy, interventional therapy, physiotherapy, psychotherapy, and comfort care, all aimed at achieving comprehensive pain management.The use of opioid should be carefully guided by scientific principles to minimize adverse effects and optimize pain relief, ultimately enhancing patients' end-of-life quality of life.

Objective:To design a novel electromagnetic ejection device for endoscopic suturing to achieve continuous deployment of suture nails.Methods:An electromagnetic ejection device and its accompanying suture nail structure were designed and a prototype was fabricated based on electromagnetic ejection principles. A finite element model of the electromagnetic ejection device was constructed to study the effects of armature-coil center distance and different driving voltages on suture nail ejection speed. An experimental platform for testing electromagnetic ejection velocity was constructed, and a high-speed camera was used to detect the ejection velocity. A platform for the suture embedding experiment was built to measure the effects of different voltages on the inserting speed of suture into the gastric wall tissue. A platform for a suture extraction force experiment was built to evaluate the extraction force of sutures embedded in tissues under different driving voltages.Results:A suture nail structure and electromagnetic ejection device were designed, and a prototype was fabricated. The ejection velocity increased and then decreased with the increase of the armature-coil center distance, and the maximum ejection velocity was 15.81 m/s at the center distance of 18 mm. At this distance, the voltage was linearly related to the ejection velocity, and the experimental values of the staple basically coincided with the simulated values. When the driving voltage was in the range of 150 to 180 V, the suture nails could successfully insert in the tissues, and the 180 V voltage group had a greater insertion depth. The extraction force of the suture nails at 120, 150, 180, and 210 V voltages were (0.49 ± 0.19), (1.14 ± 0.19), (1.23 ± 0.15), and (1.85 ± 0.31) N, respectively.Conclusions:A novel electromagnetic ejection device for endoscopic suturing is proposed that is capable of continuous firing of suture nails. This device provides a new long-distance driving method for intelligent, minimally invasive surgical instruments.

Objective: To examine the associations of fibroblast growth factor 19 (FGF19), its co-receptor KLB gene and its receptor FGFR4 with susceptibility to sarcopenia, so as to provide insights into elucidation of sarcopenia pathogenesis and formulation of precision interventions for sarcopenia. Methods: A case-control study was conducted. Patients with sarcopenia at ages of 60 years and older included in the Zhejiang Provincial Elderly Health Surveillance Cohorts were selected as the sarcopenia group, and normal residents at ages of 60 years and older were served as controls. Subjects' demographics were collected using questionnaire surveys, and the height, body weight, appendicular skeletal muscle mass and grip strength were measured. Genomic DNA was extracted from blood samples for multiplex PCR targeted capture. The associations between the KLB gene single-nucleotide polymorphisms (SNPs) and susceptibility to sarcopenia were evaluated using multivariable logistic regression models. Results: There were 200 cases in the sarcopenia group, including 91 men and 109 women, and 180 cases in the control group, including 70 men and 110 women. All SNPs satisfied the Hardy-Weinberg equilibrium, and the minor allele frequencies were all > 0.05. There were no significant differences in the distribution of SNPs between the sarcopenia and control groups (all P>0.05). Multivariable logistic regression analysis showed that the SNP rs2687968 locus in the KLB gene was significantly associated with the susceptibility to sarcopenia among the elderly men (superdominant model), and individuals carrying the AC allele had a 2.332-fold higher risk of sarcopenia than those carrying the AA/CC allele (95%CI: 1.882-3.313). Conclusions KLB gene may correlate with the susceptibility to sarcopenia among the elderly men.

Objective: To examine the effect of dietary behaviors on handgrip strength loss among the elderly, so as to provide insights into the prevention of handgrip strength loss. Methods : Based on the health surveillance cohort among the elderly in Zhejiang Province, two villages or communities were randomly sampled from each of Shaoxing and Zhoushan cities using a multi-stage cluster sampling method, and all residents that had lived in local areas for one year and longer and had an age of 60 years and older were enrolled. Participants' demographics, dietary behaviors, smoking, drinking, and exercise were collected through questionnaire surveys, and the height, body weight and handgrip strength were measured. The handgrip strength loss was diagnosed according the 2019 Consensus Update on Sarcopenia Diagnosis and Treatment proposed by Asian Working Group for Sarcopenia, and the effect of dietary behaviors on handgrip strength loss was examined using a multivariable logistic regression model. Results: A total of 1 265 residents were enrolled, with a mean age of (70.67±7.30) years, and including 565 men (44.66%) and 700 women (55.34%). The overall prevalence of handgrip strength loss was 42.85% among the participants, and the prevalence was 40.35% in men and 44.86% in women, respectively. Multivariable logistic regression analysis showed that nut intake for 1 to 3 times a week (OR=0.180, 95%CI: 0.088-0.367) and for 4 to 6 times a week (OR=0.241, 95%CI: 0.113-0.514) led to a reduced risk of handgrip strength loss among the elderly, and intake of sugary drinks for 4 to 6 times a week led to an increased risk of handgrip strength loss among the elderly (OR=2.298, 95%CI: 1.120-4.714) after adjustment for age, body mass index, educational level and exercise. Conclusion Intake of nuts and sugary drinks may affect the development of handgrip strength loss among the elderly.